Endothelial cells display an extraordinary plasticity both during development and throughout adult life. During early development, endothelial cells assume arterial, venous, or lymphatic identity, while selected endothelial cells undergo additional fate changes to become hematopoietic progenitor, cardiac valve, and other cell types. Adult endothelial cells are some of the longest-lived cells in the body and their participation as stable components of the vascular wall is critical for the proper function of both the circulatory and lymphatic systems, yet these cells also display a remarkable capacity to undergo changes in their differentiated identity during injury, disease, and even normal physiological changes in the vasculature. Here, we discuss how endothelial cells become specified during development as arterial, venous, or lymphatic endothelial cells or convert into hematopoietic stem and progenitor cells or cardiac valve cells. We compare findings from in vitro and in vivo studies with a focus on the zebrafish as a valuable model for exploring the signaling pathways and environmental cues that drive these transitions. We also discuss how endothelial plasticity can aid in revascularization and repair of tissue after damage- but may have detrimental consequences under disease conditions. By better understanding endothelial plasticity and the mechanisms underlying endothelial fate transitions, we can begin to explore new therapeutic avenues.Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with endotheliitis and microthrombosis.
To correlate endothelial dysfunction to in-hospital mortality in a bi-centric cohort of COVID-19 adult patients.
Consecutive ambulatory and hospitalized patients with laboratory-confirmed COVID-19 were enrolled. A panel of endothelial biomarkers and von Willebrand factor (VWF) multimers were measured in each patient ??48h following admission.
Study enrolled 208 COVID-19 patients of whom 23 were mild outpatients and 189 patients hospitalized after admission. Most of endothelial biomarkers tested were found increased in the 89 critical patients transferred to intensive care unit. However, only von Willebrand factor antigen (VWFAg) scaled according to clinical severity, with levels significantly higher in critical patients (median 507%, IQR 428-596) compared to non-critical patients (288%, 230-350, p?&lt;?0.0001) or COVID-19 outpatients (144%, 133-198, p?=?0.007). Moreover, VWF high molecular weight multimers (HMWM) were significantly higher in critical patients (median ratio 1.18, IQR 0.86-1.09) compared to non-critical patients (0.96, 1.04-1.39, p?&lt;?0.001). Among all endothelial biomarkers measured, ROC curve analysis identified a VWFAg cut-off of 423% as the best predictor for in-hospital mortality. The accuracy of VWFAg was further confirmed in a Kaplan-Meier estimator analysis and a Cox proportional Hazard model adjusted on age, BMI, C-reactive protein and D-dimer levels.
VWFAg is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.
VWFAg is a relevant predictive factor for in-hospital mortality in COVID-19 patients. More than a biomarker, we hypothesize that VWF, including excess of HMWM forms, drives microthrombosis in COVID-19.Receptor-interacting protein kinase 3 (RIPK3) is a multifunctional intracellular protein that was first recognized as an important component of the necroptosis programmed cell death pathway. RIPK3 is also highly expressed in non-necroptotic murine embryonic endothelial cells (ECs) during vascular development, indicating its potential contribution to angiogenesis. To test this hypothesis, we generated mice lacking endothelial RIPK3 and found non-lethal embryonic and perinatal angiogenesis defects in multiple vascular beds. Our in vitro data indicate that RIPK3 supports angiogenesis by regulating growth factor receptor degradation in ECs. We found that RIPK3 interacted with the membrane trafficking protein myoferlin to sustain expression of vascular endothelial growth factor receptor 2 (VEGFR2) in cultured ECs following vascular endothelial growth factor A (VEGFA) stimulation. Restoration of myoferlin, which was diminished after RIPK3 knockdown, rescued decreased VEGFR2 expression and vascular sprouting in RIPK3-deficient ECs after VEGFA treatment. In addition, we found that RIPK3 modulated expression of genes involved in endothelial identity by inhibiting ERK signaling independently of growth factor receptor turnover. Altogether, our data reveal unexpected non-necroptotic roles for RIPK3 in ECs and evidence that RIPK3 promotes developmental angiogenesis in vivo.In the thyroid gland, radiofrequency ablation (RFA) is being applied to both benign nodules and cancers internationally, while interest is also growing in the West. https://www.selleckchem.com/products/E7080.html Benign thyroid nodules (BTNs) may be candidates for intervention when symptoms develop. For differentiated thyroid cancers (DTC), surgery is currently the first-line treatment. However, for candidates with high surgical risk or those who refuse to undergo repeated surgery, newer techniques such as RFA are an option. Surgery is associated with complications including hypothyroidism, voice change, hypocalcemia, and a scar. RFA has been used in Asian and European institutions as an alternative to surgery, but is relatively new in North America. Although RFA is not associated with significant complications, few randomized control trials have assessed its efficacy. The studies to date suggest a low rate of severe complications and a small need for thyroid hormone replacement following RFA. Further large-scale studies focusing on a Western population ts with thyroid cancers and for selected BTNs. Additional trials with longer follow-up in North American patients are needed to validate its full role in the armamentarium of thyroid ologists.The official installation of the European Reference Networks in 2017 formed the foundation to improve quality and safety and access to highly specialized health care across the EU for patients affected by rare or low prevalence and complex conditions. The European Reference Network on Rare Endocrine Conditions (Endo-ERN) covers specific expertise from birth to senescence with a specific governance structure characterized by both a pediatric and an adult chair, and equal responsibilities for patient representatives and health care providers. The introduction on the scope and mission of Endo describes the complexity of the Endo-ERN mission and will thrive toward the ultimate aim and mission of the network of reducing health care inequalities across Europe. Specific knowledge and medical expertise of the existing rare endocrine condition is urgently needed, and therefore, raising awareness for Rare Disease Day from the Endo-ERN perspective is imperative.